Evidence map›Paper›PMID 42021299›Full record

ArticleAlzheimer's research & therapy2026

Plasma biomarker trajectories across Alzheimer's clinical onset: a 17-year prospective study.

Siqi Xie, Yumei Liang, Yana Pang, Ying Li, Shuman Cao, Yan Li, Qi Wang, Abhay Moghekar, Marilyn Albert, Jianping Jia and 1 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Siqi Xie *Innovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Xicheng District, Beijing, 100053, China.
Yumei Liang *Innovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Xicheng District, Beijing, 100053, China.
Yana PangInnovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Xicheng District, Beijing, 100053, China.
Ying LiInnovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Xicheng District, Beijing, 100053, China.
Shuman CaoInnovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Xicheng District, Beijing, 100053, China.
Yan LiInnovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Xicheng District, Beijing, 100053, China.
Qi WangInnovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Xicheng District, Beijing, 100053, China.
Abhay MoghekarDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Marilyn AlbertDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jianping JiaInnovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Xicheng District, Beijing, 100053, China. jjp@ccmu.edu.cn.
BIOCARD Study team

Funding

Project 2 MeasurementU19AG033655 · NIA · JOHNS HOPKINS UNIVERSITY · PI Abhay Moghekar · 2014 to 2026
$51.5M
Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3M
NIA NIH HHS P30 AG066507NIA NIH HHS U19 AG033655
6 · The paper itself

Abstract

backgroundLong-term trajectories of plasma biomarkers relative to clinical symptom onset in Alzheimer’s disease (AD) remain scarce.

methodsWe analyzed 17-year longitudinal data from 195 initially cognitively unimpaired participants in the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) study. Plasma biomarker trajectories were modeled as a function of years from estimated mild cognitive impairment (MCI) symptom onset using generalized additive mixed models.

resultsIn participants who progressed to amyloid-positive MCI, plasma p-tau181/Aβ42 and GFAP diverged from stable controls earliest (about 13 and 12 years before symptom onset, respectively), followed by Aβ42/Aβ40, p-tau181, and NfL, all of which became abnormal before symptom onset. Individuals who developed amyloid-negative MCI showed abnormalities only in GFAP (about 11 years before onset) and YKL-40 (around the time of symptom onset).

conclusionsThis study establishes a clinically anchored temporal map of plasma AD biomarkers. Plasma markers detect AD-related pathological changes more than a decade before symptom onset, offering a scalable, non-invasive approach for defining the preclinical phase and identifying at-risk individuals for early intervention.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersChitinase-3-Like Protein 1Disease ProgressionFemaleGlial Fibrillary Acidic ProteinHumansLongitudinal StudiesMaleNeurofilament ProteinsPeptide FragmentsProspective StudiesAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)BiomarkersCHI3L1 protein, humanChitinase-3-Like Protein 1GFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsPeptide Fragmentstau ProteinsAlzheimer’s diseaseBlood-based biomarkersLongitudinal studyTrajectory

Identifiers

PMID42021299
PMCPMC13231753

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.